This proposal focuses on the earliest interactions of the F. tularensis the causative agent of tularemia with the host. Our hypothesis is that infection of particular cells in the lung results in a different pattern of host derived immunomodulatory molecules produced that shape the host innate and adaptive immune responses to benefit the pathogen. In this study we will identify the early cells infected in lung and skin infections. We will determine the molecules produced in the earliest cells following infection using a combination of fluorescence activated cell sorting and marked bacteria. By cell purification and in vitro infection we will learn how the impact the subsequent immune response. We will then determine the F. tularensis genes responsible, and their interactions with the host. Finally, we will determine mechanism for immune modulation.